Interleukin-1 beta induces apoptosis in GL15 glioblastoma-derived human cell line

Interleukin 1-beta (IL-1 beta) induces apoptosis in a glioblastoma-derived human cell line, exhibiting a poorly differentiated astrocytic phenotype. T he apoptotic effect was demonstrated by analyzing nuclear morphology, in si tu DNA fragmentation, and by ELISA detection of cytoplasmatic nucleosomes. We correlated the degree of differentiation of GL15 cells with the apoptoti c response: 1) 4', 6-diamidino-2-phenylindole staining, combined with glial fibrillary acidic protein (GFAP) immunofluorescence, showed that the cells with apoptotic nuclei express low levels of GFAP; and 2) at 13 days of sub culture, in a more differentiated state, GL15 cells did not respond with ap optosis to IL-1 betab. In this cell line, nonrandom chromosome changes and the expression of SV40 early region have been previously shown. The involve ment of p42/p44 mitogen-activated protein kinase (MAPK) pathway in the indu ction of apoptosis by IL-1 beta was hypothesized. Previous studies have sho wn that SV40 small T antigen partially inhibits phosphatase 2A, leading to an enhancement of the steady-state activity of p42/p44 MAPK pathway. PD-098 059, specific inhibitor of p42/p44 MAPK pathway, counteracts the apoptotic effect of IL-1 beta, whereas SB-203580, specific inhibitor of p38 stress-ac tivated protein kinase (SAPK) pathway, is ineffective. The imbalance betwee n MAPK and SAPK pathways has been proposed as a key factor in determination of cell fate. Our results demonstrate that a further stimulation of p42/p4 4 MAPK pathway can constitute a death signal in tumor cells in which genomi c damage and MAPK pathway control alterations occur.